tbuckley/cabot-search huggingface dataset:
Association of baseline inflammatory biomarkers with outcomes in penile squamous cell carcinoma (pSCC) treated with immune checkpoint inhibitors (ICI).
Authors: Tony Zhuang, Subir Goyal, Jacqueline T Brown, Bradley Curtis Carthon, Omer Kucuk, Greta Russler McClintock, Lauren Beth Yantorni, Mehmet Asim Bilen, Viraj A. Master, Bassel Nazha
Journal: Journal of Clinical Oncology (2023)

11 Background: Penile squamous cell carcinoma (pSCC) is a rare neoplasm with a poor prognosis and a need for biomarkers to guide treatment selection. We report an association of baseline inflammatory markers with outcomes in pSCC treated with immune checkpoint inhibitors (ICI). Methods: We performed a retrospective review of patients with pSCC from 2012-2022 at the Winship Cancer Institute at Emory University. Demographics, disease characteristics, and optimal cutoffs of biomarkers prior to ICI initiation were described. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were obtained from complete blood count data. Clinical benefit with ICI was defined as complete response, partial response, or stable disease based on RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method and univariate Cox regression (UVA) using SAS software with significance level set at p&lt;0.05. Results: Twenty-one patients were included in which 71.4% were white and 28.6% were black. Median age at ICI initiation was 56 years (38-76). Most patients (65%) had an ECOG PS ≥2. Four patients (19.1%) had clinical benefit at best response to ICI. Most patients (76.2%) had disease progression and 14.3% were alive at last contact. Median OS was 8.4 months (mo) (95%CI: 2.3-15.7), and median PFS was 2.0 mo (95%CI: 1.3-3.2). Of 9 patients with available HPV status, 8 were HPV+. Of 12 patients with available PD-L1 status, 8 were PD-L1+. Median follow-up was 8.4 mo and median time to ICI treatment from diagnosis was 15.6 mo. High baseline NLR, MLR, PLR, and NER above optimal cut were significantly associated with shorter OS on UVA (Table,all p&lt;0.05). High baseline NLR was associated with shorter PFS (p=0.003). Baseline NLR groups were similar except for age and without differences in race, ECOG, BMI, PD-L1, and HPV status. Conclusions: Our real-world analysis reports a potential association of baseline inflammatory biomarkers with clinical outcomes in ICI-treated pSCC. More prospective and multicenter studies are needed for further confirmation. [Table: see text]
Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide.
Authors: Amarnath Challapalli, Emily Renninson, Paul White, Thiraviyam Elumalai, Omi Parikh, Alexander Vickers, Alison Jane Birtle, Andrew Brocklehurst, Rajanee Bhana, Kanchana Wickramasinghe, Kamalram Thippu Jayaprakash, Emma Gray, Matthew Sephton, Anna Bowzyk Al-Naeeb, Emily Foulstone, Alexandra Soundy, Lauren Ashurst, Amit Bahl
Journal: Journal of Clinical Oncology (2023)

335 Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular inform regarding use of next generation imaging in this setting. Methods: Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Results: 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 - 10) months. 42 patients (49.4%) had pre-treatment PSAdT of &lt;6 months and 43 (50.6%) patients had PSAdT of ≥6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT &lt;6 months but median duration had not been reached for patients with pre-treatment PSAdT ≥6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%); 21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusions: In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of &lt;6 months compared with ≥6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.
Geometry of hydrogel rectal spacer placement and risk of MRI-identified rectal wall infiltration.
Authors: Jonathan W. Lischalk, Jonathan A. Haas, Vianca F. Santos, Christopher Mendez, Astrid Sanchez, Ankur Doshi, Meredith Akerman, Jed Kaminetsky, Todd Carpenter, David Sadowsky, Aaron Katz, Herbert Lepor, Angela Tong
Journal: Journal of Clinical Oncology (2023)

312 Background: The use of rectal spacers in the management of localized prostate cancer treated with definitive radiotherapy has become ubiquitous in recent years. However, pre-treatment MRIs often identify varying degrees of hydrogel involvement within the rectal wall. In the present study, we evaluate the geometry of spacer placement and its association with radiological rectal wall infiltration. Methods: We identified all patients who underwent hydrogel rectal spacer placement in preparation for 5-fraction prostate SBRT from 1/2020 to 9/2021. Two specialty trained body radiologists evaluated all MRIs independently. Scans were evaluated for the following spacer parameters: spacer thickness, prostate-rectal distance, symmetry, and degree of rectal wall infiltration. Prostate-rectal distance was measured at the level of the prostatic apex, midgland, and base. Symmetry of the rectal spacer was measured using right or left lateralization from midgland. Degree of rectal wall invasion was categorized as follows: none, muscularis, submucosal, and intraluminal. Results: A total of 336 patients underwent MRI following hydrogel rectal spacer placement from 1/2020 to 9/2021. Patients were excluded from MRI if they had AICD/pacemaker, foreign body, or patient refusal. In those patients with any rectal wall invasion, gel thickness as measured at the base (11 vs. 10 mm, p = 0.02), midgland (14 vs. 10 mm, p &lt; 0.001), and apex (12 vs. 8 mm, P &lt; 0.001) was significantly larger than those patients without invasion. This translated into significantly larger distances between the posterior aspect of the prostate and anterior aspect of the rectum at the level of the apex (12 vs. 8 mm, p &lt; 0.001) and midgland (13 vs. 11, p &lt; 0.001), but not at the base (14 vs. 14 mm, p = 0.5). There was no association seen with asymmetrical spacer placement and rectal wall invasion (p = 0.7). Subgroup analysis of patients with more extensive invasion into the muscularis or submucosa confirmed significantly larger gel thickness at all prostate levels, as well as a larger prostate-rectal distance at the level of the apex and midgland. Significant associations remained consistent with both independent radiological evaluations. Conclusions: Hydrogel spacer rectal wall infiltration was associated with increased axial gel thickness, specifically at the level of the prostatic midgland and apex. Rectal wall infiltration was not associated with lateralization of gel. Rectal infiltration may be a result of surplus hydrogel placed particularly in the region where the potential space between the prostate and the rectum is limited.
Antitumor immunity as the basis for durable disease-free, treatment-free survival (DDFTFS) in patients with metastatic urothelial cancer (mUC).
Authors: Jonathan Forrest Anker, Sumanta Monty Pal, Seunghee Kim-Schulze, Huan Wang, Rebecca Halperin, Andrew Uzilov, Takuro Saito, Noah M. Hahn, Manishkumar Patel, Jingjing Qi, Hui Xie, Nina Bhardwaj, Sacha Gnjatic, Matt D. Galsky
Journal: Journal of Clinical Oncology (2023)

536 Background: Cisplatin-based chemotherapy has been associated with functional cures (i.e., DDFTFS) in a small subset of patients with mUC. However, the mechanistic basis for this phenomenon has remained elusive. Immune checkpoint blockade may enhance the ability of cisplatin-based chemotherapy to cure mUC, particularly if the latter is achieved by promoting antitumor immunity. From a phase II trial evaluating a phased schedule of gemcitabine and cisplatin (GC) followed by GC plus Ipilimumab (Ipi) for mUC, 4/36 patients were treatment-free disease-free &gt;7 years after initiation of treatment. We sought to identify the immunological mechanisms associated with functional cure of such patients. Methods: Whole exome sequencing was performed on pre-treatment archival tumor tissue. Neoantigen binding affinity was predicted using NetMHCcons. Neoantigen-specific T cell response was assessed via IFNγ ELISpot assays after co-culture of patient-derived peripheral blood CD4+ and CD8+ T cells with autologous neoantigen-pulsed antigen presenting B cells. Serum protein soluble analytes were measured using the Olink Target 96 Immuno-Oncology Panel at the pre-treatment, post-GC, and post-GC+Ipi timepoints. Results: CD4+ and CD8+ neoantigen-specific T cell reactivity was measured at serial timepoints in 2 patients achieving DDFTFS and 5 patients not achieving DDFTFS. Strikingly, peripheral blood CD4+ and CD8+ T cell reactivity to a predicted neoantigen emerged on cycle 6 day 1 (after 2 cycles of GC followed by 4 cycles of GC + Ipi) in 2/2 patients achieving DDFTFS (variant in TP53 or DHX9) but in 0/5 patients not achieving DDFTFS. Peripheral serum proteomic analysis at serial timepoints (n = 35 patients) revealed that pre-treatment, patients achieving DDFTFS demonstrated an immune activated phenotype with elevations in cytotoxic adaptive immunity markers and immune checkpoints (Table). After the addition of Ipi, patients achieving DDFTFS demonstrated decreased markers of tumor-promoting inflammation but increased markers of adaptive immunity, co-stimulation, and cytotoxicity. Conclusions: Anti-tumor immunity may underlie functional cures achieved in patients with mUC treated with cisplatin-based chemotherapy +/- immune checkpoint blockade. Probing the mechanistic basis for DDFTFS may facilitate the identification of pre- and on-treatment features, and therapeutic components and sequences, necessary to extend this ultimate therapeutic goal to a larger subset of patients. [Table: see text]
CaboPoint: Interim results from a phase 2 study of cabozantinib after checkpoint inhibitor (CPI) therapy in patients with advanced renal cell carcinoma (RCC).
Authors: Laurence Albiges, Thomas Powles, Anand Sharma, Balaji Venugopal, Jens Bedke, Pascale Dutailly, Bryan Qvick, Lidia Martin-Couce, Valérie Perrot, Viktor Grünwald
Journal: Journal of Clinical Oncology (2023)

606 Background: First line CPI-based therapy is the standard of care for advanced RCC. There is a lack of prospective data for cabozantinib after 1L CPI regimens, which is addressed in this study. Methods: CaboPoint (ClinicalTrials.gov identifier: NCT03945773) is an ongoing Phase 2, multicenter, open-label study of cabozantinib in adults with unresectable, locally advanced, or metastatic clear cell RCC who have progressed after 1L CPI-based therapy. Prior treatment with cabozantinib was not permitted. Patients received cabozantinib in two independent cohorts (cohort A [post nivolumab + ipilimumab] and cohort B [post CPI + vascular endothelial growth factor targeted therapy]). Both cohorts received cabozantinib (60 mg/day as starting dose) until study end (18 months after last patient’s enrollment). The primary endpoint was objective response rate (ORR) in Cohort A per RECIST 1.1 evaluated by independent central review; ORR by investigator review has been included as a secondary endpoint for both cohorts. Here we report results from the pre-planned interim analysis of ORR based on investigator assessment in both cohorts that occurred when 80% of patients in cohort A reached at least 3 months of treatment. Results: At the time of this interim analysis, 88 patients had 3 months of follow up (60 in cohort A and 28 in cohort B). Baseline characteristics were similar across cohorts. Patients had an Eastern Cooperative Oncology Group status of 0 (55.0% / 60.7%) and an intermediate or poor International Metastatic RCC Database Consortium risk (46.3% and 13.0% / 40.7% and 11.1%). The most common prior treatment in cohort B was pembrolizumab + axitinib (71.4%), followed by avelumab + axitinib (28.6%). ORR and best overall response at three months of follow-up as assessed by the Investigator are shown in the table. Conclusions: In this interim analysis, cabozantinib demonstrated preliminary efficacy in patients with advanced RCC after progression on CPI-based combination therapy, irrespective of 1L regimen. The CaboPoint trial is ongoing, with the final analysis anticipated in September 2023. Clinical trial information: NCT03945773 . [Table: see text]
Ability of STAR-CAP staging system to prognosticate risk of subsequent therapies after initial treatment of M0 prostate cancer.
Authors: Daeun Sung, Jonathan David Tward
Journal: Journal of Clinical Oncology (2023)

310 Background: Given lower mortality rates and life expectancy loss in prostate cancer, treatment regimens must consider long-term outcomes with quality of life. Aggressiveness of treatment impacts severity of side effects and depends on the highly heterogeneous staging of the disease at onset. Staging and risk-classification systems have been developed, including STAR-CAP staging system which informs prognosis and could help with treatment intensification decisions. Compared with existing models such as the AJCC, STAR-CAP had superior performance and prognostic power for disease mortality prediction. However the risk of requiring subsequent therapies (ie salvage radiation therapy or androgen deprivation therapies after initial treatment) has not been described in STAR-CAP cohorts. Quantifying risk of subsequent therapies after initial therapies is clinically useful to help patients decide between various management strategies and whether monotherapies or multi-modality therapies may be sufficient. Methods: Patients who could be stratified by STAR-CAP system and underwent surgery or radiation therapy were identified from an institutional observational registry. Patients treated before 2010 were gathered retrospectively (n=835) and prospectively thereafter (n=2588). The primary endpoint was progression to additional therapy after primary treatment (radiation, surgery, or systemic therapy). Risk of progression accounting for STAR-CAP group was estimated using the Fine and Gray Competing risk model, with death as the competing risk. P&lt;0.05 was considered statistically significant. Results: 3424 men diagnosed with prostate cancer underwent curative-intent treatment with surgery or radiation therapy (RT) between 1995 – 2022. The median age at diagnosis was 64.9 years (IQR 59.4 to 70.0); median follow-up time was 5.4 years. Patients with STAR-CAP 1A-1C had a statistically similar risk of requiring additional therapies, whereas those with 2A to 3B disease had a significantly and incrementally higher risk of requiring additional therapies (by group, hazard ratios and 95% CI: 2A, 1.8 (1.2 to 2.5); 2B, 2.9 (2.1 to 4.2); 2C, 3.4 (2.4 to 4.9); 3A, 5.7 (3.9 to 8.3); 3B, 7.0 (4.4 to 11.1), all p&lt;0.001). The 5-year risks of requiring additional therapy after surgery for a Stage 1A, 2A, and 3A patient is 9.7%, 16.2%, and 38%, respectively. The 5-year risks of requiring additional therapy after radiation with or without ADT for a Stage 1A, 2A, and 3A patient are 7.3%, 10.4% and 27.9%, respectively. Conclusions: The STAR-CAP grouping system can prognosticate risk of requiring additional therapies after primary treatment of localized prostate cancer. The lower risk of subsequent therapy seen in RT patients is likely due to use of ADT with RT. Using STAR-CAP to prognosticate risk of subsequent therapies after primary treatment can help guide treatment intensification decisions upfront.
Neoadjuvant chemotherapy plus radical cystectomy (NAC-RC) versus trimodality therapy (TMT) in early-stage small cell bladder cancer: Comparison of outcomes.
Authors: Karan Jatwani, Arya Mariam Roy, Kristopher Attwood, Anthony George, Stuthi Perimbeti, Changchuan Jiang, Muhammad Salman Faisal, Vasanthan Muthusamy Kumarasamy, Gurkamal S. Chatta, Dharmesh Gopalakrishnan
Journal: Journal of Clinical Oncology (2023)

476 Background: Small cell bladder cancer is a rare and aggressive histological variant with a paucity of data to guide the optimal management strategy in non-metastatic disease. NAC-RC and TMT (maximal transurethral resection of bladder tumor + chemoradiation) have been variably employed based on institutional preferences, and we aim to compare outcomes between these two approaches. Methods: We queried the National Cancer Database for adult patients with small cell bladder cancer diagnosed during the years 2004 to 2018. Patients with small cell histology and early-stage clinically node-negative bladder cancer (cT1-4N0M0) were included and divided into two groups based on the treatment strategy employed – NAC-RC or TMT. Patients who did not receive any definitive local therapy and those who received chemotherapy or radiation in the adjuvant setting were excluded. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 1262 patients were identified – 629 (49.8%) underwent NAC-RC while 633 (50.2%) received TMT. Patients in the NAC-RC group were younger (median 67 vs. 74 years, P &lt;0.001) and more frequently Males (81% vs 76%, p = 0.02). Clinical T stage was comparable between the groups (P = 0.38). Patients with private insurance (P &lt; 0.001) and higher income tiers (P = 0.04) were more likely to receive NAC-RC in lieu of TMT. Overall survival in the NAC-RC group was significantly longer than the TMT group (median of 41.3 vs. 25.4 months, log-rank P &lt; 0.001). On multivariable analysis, only the type of treatment modality employed was independently predictive of overall survival (Hazard Ratio of 1.22 for TMT, with 95% CI 1.05-1.43, P = 0.01). Conclusions: In early-stage clinically node-negative small cell bladder cancer, NAC-RC was associated with significantly longer overall survival compared to TMT.
Characteristics and outcomes for patients (pts) with metastatic small cell urothelial carcinoma (mSCUC).
Authors: Nathaniel R. Wilson, Jaanki Khandelwal, Lianchun Xiao, Amishi Yogesh Shah, Jianjun Gao, Sangeeta Goswami, Craig A. Kovitz, Charles Guo, Bogdan Czerniak, Christopher Logothetis, Paul Gettys Corn, Nizar M. Tannir, Arlene O. Siefker-Radtke, Omar Alhalabi
Journal: Journal of Clinical Oncology (2023)

522 Background: mSCUC is an aggressive cancer with historically poor outcomes. Methods: We performed a retrospective analysis of 216 pts with mSCUC treated at MD Anderson from 1985-2020. We captured baseline demographic and clinical characteristics, metastatic sites, systemic treatments, and survival. Median overall survival (mOS) was calculated from start of frontline (1L) therapy for metastatic disease. Results: Median age was 67 years, 84% male sex, 91% primary tumor in bladder, and 88% white race. Histology included pure SCUC (30%), predominant SCUC (44%), focal SCUC (25%) and large cell (1%). Metastatic sites were lymph nodes (54%), bone/peritoneum (39%), liver (38%), brain (31%) and lung (26%). Brain metastases frequency varied across histology (pure SCUC 48%, predominant SCUC 24.5%, focal SCUC 24%, p=0.06). Treatment regimens and mOS by frontline regimen are listed (Table). mOS was 11.91 months for treated pts with sufficient follow up (n=155). mOS by 1L treatment: EP (9.51 months), IA/EP (14.10 months), other platinum chemotherapy (13.26 months), nonplatinum chemotherapy (9.74 months), immune checkpoint inhibitor (ICI) (6.51 months), EP+ICI (undefined). Of 140 pts treated with 1L chemotherapy, 43 (31%) were able to receive second line (2L) therapy. mOS among those who received 2L chemotherapy (n=27) was 13.65 months vs those who received 2L ICI (n=16) was 22.53 months (HR=0.53, 95% CI=0.26-1.10; p=0.11). Conclusions: mSCUC is a devastating malignancy with high degree of brain involvement, and poor prognosis. 1L ICI therapy alone has suboptimal survival outcomes and a chemotherapy backbone remains necessary. A deeper understanding of SCUC’s driver biology is essential for developing better therapies. [Table: see text]
Disparities in prostate cancer diagnoses in persons experiencing homelessness.
Authors: Zachary S Mayo, Sean M. Parker, Sarah S Kilic, Jeremy Weleff, Colleen Strzalka, Michael P. Phelan, Omar Y. Mian, Kevin L. Stephans, John H. Suh, Rahul D. Tendulkar
Journal: Journal of Clinical Oncology (2023)

24 Background: We previously reported that persons experiencing homelessness (PEH) are significantly less likely to undergo prostate specific antigen (PSA) testing compared to persons not experiencing homelessness (non-PEH). The purpose of this study was to determine if reduced PSA testing in PEH results in more advanced prostate cancer diagnoses. Methods: We identified PSA screening eligible PEH (men ages 50-69) from an institutional registry of all patients that presented to our healthcare system as homeless from 2014 to 2021. A matched cohort of non-PEH was generated for comparison. Institutional CPT and HCPCS billing codes for PSA testing were available beginning 01/01/2017 and cross-referenced to identify PEH and non-PEH who underwent PSA testing at least once between 01/01/2017 and 12/31/2021. In patients with ≥ 1 PSA test, we recorded screening, oncologic and treatment related variables. Patients with a history of prostate cancer diagnosed outside the study timeframe were excluded. Results: A total of 9,249 PEH were identified, with 1,597 meeting PSA screening criteria during the study timeframe; 3,370 screening eligible non-PEH were available for comparison. The median age was 59.0 for PEH and 60.0 for non-PEH. PEH were significantly less likely to have a primary care provider (58% vs 81%, p&lt;0.001) or to have a PSA test (12% vs 33%, p&lt;0.001). Among patients with a PSA test, PEH were significantly less likely to have multiple PSA tests compared to non-PEH (28% vs 61%, p&lt;0.001) and significantly more likely to have a PSA ≥ 4.0 (18% vs 12%, p=0.028). In patients with a PSA ≥ 4.0, PEH were less likely to receive a prostate biopsy (37% vs 61%, p =0.009) and there was a trend towards decreased prostate MRI (11% vs 25%, p=0.085). A total of 6 PEH (0.4%) and 46 non-PEH (1.4%) were diagnosed with prostate cancer. The median PSA at diagnosis was 12.6 in PEH vs 7.0 in non-PEH (p=0.052). PEH were significantly more likely to present with high/very high risk disease (4/6 [66%] vs 9/46 [20%], p=0.019); no PEH had very low/low risk disease compared with 20 (43.5%) non-PEH. PEH were more likely to present with lymph node positive or metastatic disease (3/6 [50%] vs 3/46 [7%], p=0.016). The median time from biopsy to treatment was 119 days in PEH and 76 days in non-PEH (p=0.391). Conclusions: PEH are less likely to receive prostate cancer testing following an elevated PSA and more likely to present with high risk advanced prostate cancer. Interventions to increase prostate cancer awareness in PEH are needed to reduce disparities.